Hitherto extensive use has been made of polymers in the synthesis of linear peptides and oligonucleotides. The advantage of these methods is that high yields can be obtained in each step of the synthesis by using a large excess of either soluble or insoluble reagent. The desired products can be easily separated from excess of reactants by filtration of the resin.
The alpha-alkylation of carboxylic esters having more than one alpha-hydrogen is accompanied generally by an extensive ester condensation, and to varying degrees by dialkylation. Some solutions have been offered, such as the use of t-butyl esters with lithium amide as base in liquid ammonia. It has also been shown that metalated carboxylic acids and 2-oxazoline derivatives of acids undergo alkylation without condensation.
In conventional acylations of esters having more than one alpha-hydrogen with acyl halides or anhydrides, at least two competing reactions take place resulting in the formation of the self-condensation product of the ester and the diacylated ester. Such competing reactions are undesired as a mixture of products is obtained. It is possible to carry out the reaction in very dilute solutions, but this too is inconvenient and expensive.